TY - JOUR
T1 - Inclusion bodies: Specificity in their aggregation process and amyloid-like structure
AU - Morell, Montse
AU - Bravo, Ramona
AU - Espargaró, Alba
AU - Sisquella, Xavier
AU - Avilés, Francesc X.
AU - Fernàndez-Busquets, Xavier
AU - Ventura, Salvador
PY - 2008/10/1
Y1 - 2008/10/1
N2 - The accumulation of aggregated protein in the cell is associated with the pathology of many diseases and constitutes a major concern in protein production. Intracellular aggregates have been traditionally regarded as nonspecific associations of misfolded polypeptides. This view is challenged by studies demonstrating that, in vitro, aggregation often involves specific interactions. However, little is known about the specificity of in vivo protein deposition. Here, we investigate the degree of in vivo co-aggregation between two self-aggregating proteins, Aβ42 amyloid peptide and foot-and-mouth disease virus VP1 capsid protein, in prokaryotic cells. In addition, the ultrastructure of intracellular aggregates is explored to decipher whether amyloid fibrils and intracellular protein inclusions share structural properties. The data indicate that in vivo protein aggregation exhibits a remarkable specificity that depends on the establishment of selective interactions and results in the formation of oligomeric and fibrillar structures displaying amyloid-like properties. These features allow prokaryotic Aβ42 intracellular aggregates to act as effective seeds in the formation of Aβ42 amyloid fibrils. Overall, our results suggest that conserved mechanisms underlie protein aggregation in different organisms. They also have important implications for biotechnological and biomedical applications of recombinant polypeptides. © 2008 Elsevier B.V. All rights reserved.
AB - The accumulation of aggregated protein in the cell is associated with the pathology of many diseases and constitutes a major concern in protein production. Intracellular aggregates have been traditionally regarded as nonspecific associations of misfolded polypeptides. This view is challenged by studies demonstrating that, in vitro, aggregation often involves specific interactions. However, little is known about the specificity of in vivo protein deposition. Here, we investigate the degree of in vivo co-aggregation between two self-aggregating proteins, Aβ42 amyloid peptide and foot-and-mouth disease virus VP1 capsid protein, in prokaryotic cells. In addition, the ultrastructure of intracellular aggregates is explored to decipher whether amyloid fibrils and intracellular protein inclusions share structural properties. The data indicate that in vivo protein aggregation exhibits a remarkable specificity that depends on the establishment of selective interactions and results in the formation of oligomeric and fibrillar structures displaying amyloid-like properties. These features allow prokaryotic Aβ42 intracellular aggregates to act as effective seeds in the formation of Aβ42 amyloid fibrils. Overall, our results suggest that conserved mechanisms underlie protein aggregation in different organisms. They also have important implications for biotechnological and biomedical applications of recombinant polypeptides. © 2008 Elsevier B.V. All rights reserved.
KW - Amyloid fibrils
KW - Conformational diseases
KW - Inclusion bodies
KW - Protein aggregation
KW - Protein folding
U2 - https://doi.org/10.1016/j.bbamcr.2008.06.007
DO - https://doi.org/10.1016/j.bbamcr.2008.06.007
M3 - Article
VL - 1783
SP - 1815
EP - 1825
JO - Biochimica et Biophysica Acta - Molecular Cell Research
JF - Biochimica et Biophysica Acta - Molecular Cell Research
SN - 0167-4889
ER -